Early onset high myopia and severe anisometropia associated with familial exudative vitreoretinopathy of irregular dominant inheritance in 12 Chinese families:analysis of refraction features and pathogenic variations

Author:

Cheng Wanyu1,Rong Weining2,Li HuiPing2,Wang Xiaoguang2,Qi Rui3,Qi Xiaolong2,Sheng Xunlun2,Chi Wei1

Affiliation:

1. The First Hospital of Lanzhou University, The First Clinical Medical College of Lanzhou University

2. Ningxia Eye Hospital, People’s Hospital of Ningxia Hui Autonomous Region, Third Clinical Medical College of Ningxia Medical University

3. Hubin Aier Eye Hospital

Abstract

Abstract

Purpose Familial exudative vitreoretinopathy (FEVR) is a hereditary blinding vitreoretinopathy characterized by anomalous retinal vascularization. In the early stages, patients are mostly asymptomatic and prone to missed diagnosis because the lesion is located in the peripheral part of the retina. Early-onset high myopia and severe anisometropia are often the earliest reasons for ophthalmologic consultation in FEVR patients. However, there are few studies on the genetic variants and clinical phenotypes associated with eoHM-FEVR and anisometropia-FEVR patients. The purpose of this study was to screen the pathogenic variations in 12 FEVR families and analyze the refractive status and pathogenic genes in patients with irregular dominantly inherited FEVR. Methods the patients with clinical diagnoses of eoHM-FEVR or anisometropia-FEVR were evaluated from October 2019 to August 2022. Comprehensive ophthalmic tests were performed on participants to confirm the phenotype. The genotype was identified using whole exon sequencing, and further verified the results among other family members by Sanger sequencing. Normal protein structures were constructed with alphfold, and mutant proteins were visualized and analyzed with pymol software. The pathogenicity of the variants was determined in accordance with the guidelines of the American College of Medical Genetics and Genomics (ACMG). The protein-protein interaction (PPIs) network analysis with STRING and k mean clustering was applied for detecting the interacting of genes in the candidate genes and the ClusPro Server was used for protein-protein docking. Results A total of 12 FEVR families were included in the study, and all the probands were found to have high myopia in both eyes or one eye before the age of 7 years. The pathogenic variants were identified in the genes TSPAN12, LRP5, VCAN, and FZD4 known to be associated with FEVR in 7 probands. FFA examination found that FEVR patients in all families showed the onset of the disease earlier than the previous generation, and the disease gradually worsened. It should be noted that the FEVR probands in all families showed an earlier age of onset than the previous generation and a more severely fundus abnormalities in the fundus examination and fluorescin angiography. Among them, 3 probands had severe anisometropia and asymmetric fundus changes in both eyes and showed the higher the degree of myopia, the worse the best corrected visual acuity and the more serious the degree of FEVR. Cluster analysis show 13 eoHM related gene blong to 3 cluster, which belong to collagen-containing extracellular matrix cellular component, endosome lumen and Wnt signaling pathway respectively. Among the 13 eoHM related genes, FZD4 and LRP2 encode protein can dock by together analyzed by ClusPro software, the same to VCAN and FBN1 encoding protein. The complex protein, FZD4-LRP2 and VCAN-FBN1 play a bridge role among eoHM related gene according to PPI network analysis. Conclusion In this study, the FEVR families showed the phenomenon of irregular dominant inheritance. The asymmetric FEVR manifested as severe anisometropia and the eye with the higher myopia tends to have a more heavily staged FEVR and more pronounced fundus changes. PPIs network analysis revealed important modules of gene interacting and FZD4-LRP2 and VCAN-FBN1 complex protein were potentially related to high myopia development. For patients with high myopia or with obvious anisometropia in both eyes, more attention should be paid clinically to comprehensive examination of the peripheral fundus and early genetic testing.

Publisher

Springer Science and Business Media LLC

Reference43 articles.

1. Familial exudative vitreoretinopathy;Criswick VG;AM J OPHTHALMOL,1969

2. Familial Exudative Vitreoretinopathy: Pathophysiology, Diagnosis, and Management;Tauqeer Z;Asia Pac J Ophthalmol (Phila),2018

3. Diversity of retinal vascular anomalies in patients with familial exudative vitreoretinopathy;Kashani AH;Ophthalmology,2014

4. XiangHu, YiqianFei, PingXu, YuPeng, JieZhao, Peiquan.Clinical and genetical features of probands and affected family members with familial exudative vitreoretinopathy in a large Chinese cohort[J];Wang SZ;Br J Ophthalmol,2021

5. Ranchod TM, Ho LY, Drenser KA, Capone AJ, Trese MT. Clinical presentation of familial exudative vitreoretinopathy. OPHTHALMOLOGY 2011, 118(10):2070–2075.

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3